Governments at all levels seek to provide optimal healthcare for Canadians. Pressures of an aging population and, with it, the rise of HONDA diseases, planning for emerging infectious diseases and global pandemics contribute to budget impacts that payers must address.
The biotech sector provides solutions to improve patient access to novel treatments. There are new vaccines and biologics, the discovery of the causes and potential treatments of rare diseases and precision and personalized medicine that results from advances in genetic sequencing and mapping technology, gene editing and stem cell research. These solutions provide improved health outcomes while addressing budget constraints within the healthcare system. As such they benefit patients, their families and all of Canadian society.
The biotech ecosystem is committed to continuing a constructive, evidence-based dialogue with Canadian governments to ensure the best possible health outcomes for Canadians. It works collaboratively with payers, healthcare providers and policy makers to realize the potential of 21st-century medicines while maximizing patient benefit and driving efficient spending.
Soricimed – Diagnostics and Drug Candidates for Cancer
Soricimed Biopharma is a clinical-stage pharmaceutical company based in Sackville, NB developing cancer therapeutics and diagnostic tools for private industry.
When Dr. Jack Stewart was a professor at Mount Allison University, he characterized a peptide in the saliva of the northern short-tailed shrew capable of paralyzing the animal’s insect prey. The bi-functional paralytic peptide, soricidin, modulates ion channels and shows promise in the treatment of pain and cancer. Stewart’s lab went on to show that the two effects were caused by separate domains of the protein.
The company’s oncology management platform includes the development of a blood test that uses the peptide to detect, locate and monitor or confirm early stages of ovarian, breast and prostate cancers. Soricimed collaborates with the Atlantic Cancer Research Institute to develop this diagnostic tool.
Soricimed partners with other external collaborators – universities, the BC Cancer Agency, various National Research Council labs, contract research organizations and regulatory and clinical consultants to develop its pipeline and assist the move to clinical testing.
The FDA has granted orphan drug status to the company’s peptide SOR-C13 for the treatment of both ovarian and pancreatic cancers. As an orphan drug, if approved for use, it may qualify for market exclusivity for seven years in the US.
Canadian Centre for Regenerative Medicine
A not-for-profit organization, the CCRM supports its network of industry partners, institutions and advisors to make Canada a global leader in the development and commercialization of regenerative medicine technologies and cell and gene therapies. The organization facilitates collaborations to use stem cells, biomaterials and molecules to treat damaged tissues and treat disease.
Western University and an HIV Vaccine
The world’s first HIV vaccine, developed in the lab of Chil-Yong Kang at Western University in London, is ready to enter Phase 2 clinical trials after it was shown to be safe and effective in eliciting an immune response in HIV-positive patients. The clinical tests are being undertaken in partnership with Sumagen Canada.
Immunovaccine – Vaccine Delivery
This Halifax-based immuno-oncology company develops vaccines for cancer and other diseases. It began by developing veterinary vaccines before translating its research to create DepoVax™, its vaccine delivery platform for humans. It has multiple oncology vaccines in Phase 1 and 2 clinical trials and has an RSV vaccine that has completed Phase 1 trials. Immunovaccine collaborates with industry partners to develop vaccines against malaria and Zika virus.
Parvus Therapeutics – Partnering with Big Pharma to Accelerate Drug Development
This Calgary company’s Navacim™ technology generates potential breakthrough biologics for autoimmune diseases, including Type I diabetes and multiple sclerosis. Navacims are nanoparticles designed to suppress T cells that cause an autoimmune disease. Parvus signed a deal with Novartis in April 2017 in which Parvus will continue to conduct preclinical work on its promising Type I diabetes drug while Novartis will usher the candidate through clinical trials and bring it to market. Novartis gets exclusive, worldwide rights to the technology for Type 1 diabetes patients.
A clinical-stage pharmaceutical company seeking treatments in nephrology and autoimmunity. Its lead drug candidate is the calcineurin inhibitor Voclosporin, a potential treatment for lupus nephritis that has entered Phase 3 clinical trials. The drug was granted fast-track status by the FDA.
The Need for Rapid Production of Flu Vaccines
When an outbreak of a contagious illness such as the H1N1 influenza pandemic of 2009 hits, it is essential that healthcare providers have access to safe and effective vaccines. Conventional vaccine production, which uses proteins expressed in bacteria, yeast, mammalian cell cultures or eggs, is complicated, expensive and takes six months. That’s why Medicago, a biotechnology company in Quebec City, turned to plant-based vaccine production. In 2012, as part of the pandemic preparedness of the Defense Advanced Research Projects Agency (DARPA is an agency of the US Department of Defense), Medicago successfully prepared more than ten million influenza H1N1 vaccines in only one month.
Medicago accelerates the development of vaccines for influenza and other illnesses using plant-based expression of antigens in transgenic tobacco plants. This speed is essential to produce enough vaccine quickly enough to meet the first wave of a pandemic.
The process uses tobacco plants as protein factories. Tobacco was the first transgenic plant and current plant-based gene expression systems are more adaptable, allow faster vaccine development and are less expensive to scale up than conventional mammalian expression systems.
The tobacco is seeded in greenhouses. Large-scale robotics move the seedlings, which are transformed with genetic material via vacuum infiltration. The plants are incubated for four-10 days, then harvested to extract proteins that are purified to produce vaccine-grade product. Medicago plant-based vaccines are made from virus-like particles, not mutated whole viruses cultured in eggs, and have good yields and require lower dosages. To meet emergency demand or enter an emerging market, scale-up is as quick as building more greenhouse-based manufacturing facilities.
Vaccine and Therapeutic Protein Pipeline
Medicago’s seasonal quadrivalent flu vaccine and pandemic vaccine are currently in Phase 2 clinical trials. It is conducting preclinical research and development on plant-based vaccines against rotavirus, HPV, Norwalk virus, anti-Ebola monoclonal antibodies and therapeutic proteins.
In 2013 the US Department of Defense contracted Medicago to rapidly produce a vaccine candidate for the H7N9 strain of influenza. The company has produced Ebola monoclonal antibodies against the Zaire strain for the Biomedical Advanced Research and Development Authority (BARDA is a US government agency) and in 2015 the Public Health Agency of Canada contracted Medicago to produce antibodies to the Sudan strain of the Ebola virus.
Medicago opened a new production complex in Quebec City in 2015 with a capacity of 40-50 million doses of seasonal flu vaccines. The complex houses its head office, R&D facilities and commercial production. It aims to produce 10 million doses of pandemic flu vaccine per month and 2.5 million of quadrivalent seasonal flu vaccine per month at its 97,000 sq. ft. facility in North Carolina.
ZYMEWORKS of Vancouver and global multinational partnerships
A globally competitive biotechnology sector in Canada provides high-skilled jobs, new medical therapies and economic growth. The success of biotech companies can follow different trajectories. One model is the development and acquisition model, in which a startup creates an attractive product and finds a buyer. Enobia Pharma and Cynapsus Therapeutics exemplify Canadian successes at attracting lucrative deals. [See sidebar]
The second model is for companies that prefer to remain Canadian-owned while maintaining their leadership position in the sector. These biotech entrepreneurs need to attract stable, long term financing so they can expand while nurturing their product pipelines. Forming strategic partnerships with large pharmaceutical companies is one way of doing this and Zymeworks is a company that has proven successful. The Vancouver biotherapeutics company offers a good model for how to attract venture capital, as well as work with corporate investors, to further its internal R&D and grow the company.
Zymeworks develops targeted protein biotherapeutics, especially in areas of unmet medical need, for cancer, autoimmune and inflammatory diseases. But it is Zymeworks’ drug development platforms that have attracted the attention of major pharmaceutical players around the world and provided the company with the capital it needs to explore its internal pipeline of potential drug remedies.
These tools include molecular modeling software for optimizing protein structure. They are able to engineer thousands of variant proteins to test as potential cancer treatments. Promising candidates can then be modified to improve their function. The Azymetric™ platform is protein modeling and structure-guided optimization technology that propels drug development. It designs bispecific monoclonal antibodies, which are capable of recognizing two distinct antigen markers. These can be on the same or different cells and can increase the specificity of a drug’s action. The company’s EFECT™ platform creates a library of antibodies with Fc modifications that can be tested for up- and down-regulation of the immune response.
A Hybrid Business Model
Big Pharma has moved away from consolidating all its functions – head office, R&D facilities and manufacturing – in one spot. Instead, firms seek to partner with small- and medium-sized biotechnology enterprises like Zymeworks to further their drug development and commercialization needs.
Zymeworks has a reputation for striking corporate partnerships with these big players in the pharmaceutical industry, which are mostly attracted to the Azymetric drug development platform. Zymeworks made a licensing deal with Merck in 2011 worth $187 million, signed a research pact worth up to $1 billion with GlaxoSmithKline in 2016, has two deals with Eli Lilly worth $375 million and partnerships with Celgene and with Daiichi-Sankyo, which licenses both the Azymetric and EFECT platforms.
The beauty of this hybrid business model is that it allows Zymeworks to use the influx of capital to further its internal drug development pipeline, usher biologics through clinical trials and hopefully bring these drugs to market.
Promising Drug Candidate Pipeline
Its drug candidates include ZW25, a potential breast cancer treatment. ZW25 is a bispecific antibody that is currently in adaptive Phase 1 clinical trials. Based on the company’s Azymetric platform, the protein latches onto two distinct regions of HER2 – the human epidermal growth factor 2 receptor – targeting any cancer expressing HER2, including those with low HER2 expression.
ZW35 is an antibody drug conjugate based on ZW25 but with an attached cytotoxic payload. The antibody recognizes the HER2 receptor on a cancer cell, is internalized and releases its payload, killing the cell. It targets diseases in which HER2 is expressed, including breast and ovarian cancers, especially for disease that is refractory to HER2-targeting drugs such as Kadcyla. ZW35 was granted Orphan Drug status by the FDA for treatment of ovarian cancer.
Academic and Government Partners
The company collaborates with scientists at UCLA to investigate the clinical effects of Zymeworks’ bispecific antibodies as well as with researchers at the University of Victoria and the British Columbia Cancer Agency on developing engineered cytokine and cytokine receptor pairs.
Zymeworks partners with the National Research Council of Canada (NRC) to develop therapeutic antibody platforms and protein-based therapeutic candidates.
The biotech company, which is backed by venture capital and corporate investors, went public in April on both the TSE and NYSE with the first Canadian tech IPO since 2015. The capital raised positions the company to further its product development goals and for more growth. Zymeworks recently opened a second building in Vancouver, a 929-square metre research facility.
Model 2 – Funding the next great idea
A private biopharmaceutical company with favorable preclinical data for drugs in its pipeline attracts the attention of Big Pharma. For a company committed to staying the course and growing in Canada – like Zymeworks – the resources and expertise of a multinational are invaluable. In other cases, a company might choose to sell its assets outright. Here are two recent success stories that followed this second model.
Enobia’s Valuable Discovery
Hypophosphatasia is a rare, life-threatening bone disease that was first reported in the literature by a researcher at the University of Manitoba in 1936. It had no treatment before the Montreal-based Enobia Pharma developed Strensiq, the first enzyme replacement therapy for the disease. The company had promising preclinical data, but its president, Robert Heft, knew they would have trouble getting the drug in the hands of patients without the capital and expertise of a larger company. Alexion acquired Enobia for $1.1 billion in 2012 in the largest private pre-commercial sale of a biopharmaceutical company. Alexion then shepherded Strensiq through clinical trials and the treatment won FDA approval in 2015.
Robert Heft continues his 30-plus years in the industry and currently sits on the board of Clementia, a Montreal-based pharmaceutical firm committed to developing treatments for rare diseases.
Cynapsus Therapeutics (now Sunovion)
Cynapsus was another Canadian biopharmaceutical company with a promising lead product that proved attractive to Big Pharma. APL-130277 is a sublingual drug to treat symptoms of Parkinson’s disease. In early 2016, Cynapsus entered a Phase 3 clinical trial, collaborating with the Michael J Fox Foundation to incorporate wearable devices and Intel’s big data analytics into the study. In September 2016, Sunovion Pharmaceuticals paid $624 million for Cynapsus and APL-130277. Sunovion hopes to apply for drug approval in 2017.